Considerable attention has focused on the development of cell-based therapies. For example, one type of cell-based therapy includes removing cells or tissue from an individual, manipulating the tissue ex vivo, and returning the cells to the individual. Treatments include the use of lymphokine activated killer (LAK) cells (see U.S. Pat. No. 4,690,915 issued to Rosenberg), tumor infiltrating lymphocytes (TIL) cells (see U.S. Pat. No. 5,126,132 issued to Rosenberg), cytotoxic T-cells (see U.S. Pat. No. 6,255,073 issued to Cai, et al.; U.S. Pat. No. 5,846,827 issued to Celis, et al.), expanded tumor draining lymph node cells (see U.S. Pat. No. 6,251,385 issued to Terman), genetically transformed stem cells (see U.S. Pat. No. 6,225,044 issued to Klein, et al.), mononuclear phagocytes (see U.S. Pat. No. 6,210,963 issued to Haddada, et al.), lymphocytes (see U.S. Pat. No. 6,194,207 issued to Bell, et al.; U.S. Pat. No. 5,443,983 issued to Ochoa, et al.; U.S. Pat. No. 6,040,177 issued to Riddell, et al.; U.S. Pat. No. 5,766,920 issued to Babbitt, et al.), dendritic cells (see U.S. Pat. No. 6,210,662 issued to Laus, et al.), lymphocytes treated with oxidizing agents (see U.S. Pat. No. 6,204,058 issued to Bolton), and cellular vaccines (see U.S. Pat. No. 6,227,368 issued to Hiserodt, et al).
The U.S. Food and Drug Administration (FDA) refers to these therapies as “Somatic Cell and Gene Therapies”. As defined by the FDA, a “somatic cell therapy product” can be one or more autologous (self), allogeneic (intra-species), or xenogeneic (inter-species) cell(s) that have been propagated, expanded, selected, pharmacologically treated, or otherwise altered in biological characteristics ex vivo to be administered to humans and applicable to the prevention, treatment, cure, diagnosis, or mitigation of disease or injuries. A “gene therapy product”, as defined by the FDA, can be one or more products that contain genetic material which are administered to modify and/or manipulate expression of genetic material and/or to alter biological properties of living cells.
The gap between the need for replacement of damaged or diseased organs in patients, with otherwise significant life-expectancy, and the supply of donor organs is growing at an ever increasing rate (Gridelli and Remuzzi, 2000). Tissue bioengineering and in vitro organogenesis research have the potential to bridge this gap. The availability of stem cells for organs in demand would greatly accelerate progress in these efforts.
A major obstacle to cell-based therapies is the availability of sufficient numbers of the desired cell type. Even in instances where it is possible to select for relatively purer populations such as hematopoietic stem cells (for example by cell sorting), these populations typically do not expand when cultured.
Accordingly, methods to expand cells ex vivo, particularly without significant alteration, are highly desirable. The ability to expand populations of cells, including a variety of stem cells as well as adult cells such as fibroblasts, beta cells, and cells of the immune system, would greatly contribute to cell-based therapies such as bone marrow transplants, gene therapies, tissue engineering, and in vitro organogenesis. Production of autologous stem cells to replace injured tissue would also reduce the need for immune suppression interventions. Considerable difficulty in achieving this objective has been encountered, thus far.
Thus, despite the need for methods to expand cells from an individual, including methods to expand them ex vivo, it has not been possible to readily do so.